Cancer is a multi-faceted disease in which a group of cells display uncontrolled growth, invasion that intrudes upon and destroys adjacent tissues, and sometimes metastasis, or spreading to other locations in the body via lymph or blood. These three malignant properties of cancers differentiate them from benign tumors, which do not invade or metastasize.
Lung cancer—predominantly non-small lung cancer (NSCLC)—is the first cause of cancer deaths worldwide, resulting in about 1 million deaths each year. Its incidence increases especially for non-smoking women. Despite advances in prevention, screening, resection methodology and chemotherapy strategies, only about 15% of patients survive more than 5 years.
The selection of an appropriate treatment is crucial for the patient. It is essential to know when to use immediately a heavy and aggressive treatment protocol in order to prevent extension of an aggressive cancer. In contrast, performing a heavy and aggressive treatment when it is not necessitated by the tumor carried by the patient is also disadvantageous for the patient. Indeed, heavy and aggressive treatments always lead to adverse toxicities that may significantly affect the patient's quality of life. In addition, such heavy and aggressive treatments are usually very costly, and should thus be performed only when it is necessary.
Currently, treatment selection for solid tumors is based on tumor staging, which is usually performed using the Tumor/Node/Metastasis (TNM) test from the American Joint Committee on Cancer (AJCC). The TNM system assigns a number based on three categories. “T” denotes the tumor size, “N” the degree of lymphatic node involvement, and “M” the degree of metastasis. The broader stage of a cancer is usually quoted as a number I, II, III, IV derived from the TNM value grouped by prognosis; a higher number indicates a more advanced cancer and likely a worse outcome.
It is commonly acknowledged that, while this test and staging system provides some valuable information concerning the stage at which solid cancer has been diagnosed in the patient, it is imprecise and insufficient. In particular, it fails to identify the earliest stages of tumor progression. In addition, the TNM test does not give information on the tumor aggressiveness and its usefulness for prognosis is thus limited. According to clinicians and pathologists, the current clinical staging “Tumor Node Metastasis” (TNM) system is thus not sufficient for predicting the outcome of patients.
There is a real need for better prognosis tests of cancer, not only to improve patient global survival, but also to improve their quality of life and to keep aggressive and costly chemotherapies for patients who will really benefit from them. In particular, there is a need for novel robust prognosis markers which can be used reliably for the prognosis of lung cancer.
In an attempt to identify predictors of patient prognosis and response to therapy, many studies profiling gene expression in lung cancer have been completed or are in progress. So far, these genetic tests add modest prognostic information to standard prediction methods. Indeed these multi-gene signatures were mostly obtained from unbiased micro-array based screenings of thousands of genes and therefore mostly include “endpoint” selected cell proliferation-related genes i.e. genes that drive at the latest stages of tumorigenesis either cell cycle progression or tumor differentiation. However these two latter features were already estimated by the standard clinico-pathological markers e.g. histological grade, mitotic count, Ki67 index, etc., which also capture the proliferation status
Since the conventional clinical staging classification is not sufficient to predict the survival of patients who suffer from lung cancer, additional prognostic factors are needed to better forecast their outcome. The present inventors have shown that a DNA replication stress signature is a predictor of the cancer survival.